Many chemotherapeutic anti-cancer agents, known to the prior art in Pharmaceutical Sciences by Remington, 15th Ed., pages 1074 to 1086, 1975, published by the Mack Publishing Co., Easton, Pa., are indicated as having a certain degree of usefulness for the management of neoplastic diseases, particularly against neoplastic cells. However, the use of these agents is often limited because of their detrimental toxic effects on normal tissues. The effectiveness of these anti-tumor agents can be improved by methods altering their distribution in the body to increase their local concentration at the tumor cell site. In this manner, the selectivity of their chemotherapeutic effect for tumor cells may be enhanced in the body.
For example, the prior art has reported that some anti-tumor drugs may be bound convalently to macromolecules without concomitant loss of activity, and that non-covalent complexes or mixtures of the drug and anti-tumor antibodies may be more efficient than the drug alone. Also, it has been shown as reported in Cancer Research, Vol 35, pages 1175 to 1181 and 1182 to 1186, 1975, that the potent anti-tumor antibiotics daunomycin and adriamycin can be linked covalently to immunoglobulins with retention of their activities. The cytotoxic activity of these drug-antibody conjugates as tested in vitro on tumor and normal cell cultures was found to be similar to that of the free drug, and a significant amount of antibody activity was retained. When conjugates of daunomycin with immunoglobulines directed against either of two lymphoid tumors were tested for their toxic effects on various tumor target cells, it was found that the drug preferentially affected those target cells which the antibodies could recognize.